Project H: Causal Modeling of Genetic Systems; Gary A Churchill (Jackson) Mathematical modeling is a defining feature of systems biology. Of the many available approaches to modeling, graphical models [117; 118] are unique in their promise to reveal causal relationships and thus to predict response to perturbations based on the correlation structure of multivariate data. Directed graphical models can be inferred from genetic data using genotype as a causal anchor [119;120]. The questions posed here are whether these genotype-driven graphical models can make valid predictions of phenotype and to what extent do the inferred graphical structures reflect the underlying network of biochemical reactions.